JACK W. SZOSTAK PRESENTS 2010 BLOCH LECTURE

by
Andrew Murray

November 15th, 2010

Jack W. Szostak was born in London and raised in Canada. He started college at McGill when he was 15 and began his PhD work at Cornell four years later, focusing on Eudorina a colonial relative of the single celled alga Chlamydomonas reinhardtii. But instead of completing this project, Jack and a fellow student, John Stiles, worked in the lab of Ray Wu to make a synthetic oligonucleotide that could detect both the gene and the mRNA for cytochrome c1, which was then the only part of the budding yeast genome whose DNA sequence was known.

Jack stayed in the Wu lab for his post-doc and worked in close collaboration with Rodney Rothstein to develop methods to manipulate the yeast genome in ways that would give information about the structure and function of chromosomes. He started his own lab at the Dana Farber Cancer Institute in 1979 and produced a series of remarkable discoveries with his students and collaborators: they showed that double stranded breaks in DNA could direct recombination and proposed that meiotic recombination was induced by DNA breaks, they produced the first artificial chromosomes and used them to infer that the linkage between sister chromatids was topological, and Jack and Liz Blackburn collaborated to show that the telomeres from Tetrahymena could function in budding yeast. On this last project, Jack performed the key experiments himself, and his, Liz Blackburn, and Carol Greider's contributions to understanding the ends of chromosomes were rewarded with the 2009 Nobel Prize in Physiology or Medicine.

In 1984, Jack moved from the Dana Farber Cancer Institute to become one of the first members of the Department of Molecular Biology at Massachusetts General Hospital. At the same time, he became interested in the role that small RNA molecules seemed to have played in the origin of life and his lab gradually switched from studying the molecular genetics of yeast to the function and evolution of small RNA molecules. Again, a long list of impressive discoveries appeared including the in vitro selection of RNA molecules with a wide range of chemical activities, one of which was eventually evolved into an RNA polymerase, the development of methods to select for interesting proteins that were still attached to the RNA molecules that encoded them, and the development of lipid based protocells that used entirely physical processes to grow and divide. Jack's current work focuses on combining work on self-replicating RNA and protocells to produce a fully self replicating proto-organism that might look something like the origin of life.

The Bloch lecture, sponsored by Pfizer, honors Harvard faculty member and Nobel-prize recipient Konrad Bloch (1912-2000), a pioneer in the field of cholesterol and lipid metabolism.

by Jim Henle

Konrad E. Bloch was an outstanding scientist who helped shape the discipline of biochemistry in its formative years. One of the founders of biochemical studies at Harvard, he was part of the pioneer generation that included George Wald, Paul Doty, John Edsall and Frank Westheimer. Best known for his studies of cholesterol, he was awarded the Nobel Prize in Medicine or Physiology in 1964 (shared with Feodor Lynen) for investigations in the mechanism and regulation of cholesterol and fatty acid metabolism. Especially noteworthy were the studies on the biological synthesis of the molecule and, according to the Nobel Prize website, “on various aspects of terpene and sterol biogenesis…enzymatic formation of unsaturated fatty acids and...in various aspects of biochemical evolution.”

Arriving at Harvard from the University of Chicago in 1954, he was appointed Higgins Professor of Biochemistry, a position he held until his retirement in 1982. He was part of the core group at Harvard that founded the Committee on Higher Degrees in Biochemistry. With the somewhat later arrival of James Watson, Matthew Meselson, Walter Gilbert, Mark Ptashne and Guido Guidotti, Harvard had achieved a remarkably dynamic and productive core group in biochemistry and molecular biology, of which Dr. Bloch was a signal part. The late Dean Jeremy Knowles described him as “a marvelously perceptive biochemist and a wise, generous and cultivated man who forged the connections between chemistry and biochemistry. He was one of that distinguished line of European biochemists whose deep understanding of metabolism laid the chemical foundations of today’s biology.” [quoted in Harvard Gazette, Oct. 19, 2000]

Dr. Bloch was born in Neisse, then part of Germany, in 1912; he was racially excluded from his studies at Munich in 1934 upon the Nazi advent to power. His subsequent odyssey began in Switzerland, and he was spared a likely fatal return to Germany by the intervention of John Anderson, a Yale biochemist, who helped him with a visa to the US. In America, his studies resumed at Columbia; after a brief stay in Chicago, he came to Harvard.

His work was widely recognized; in addition to the Nobel, he received the US National Medal of Science, and many other awards and honorary degrees. In addition to his scientific output, he wrote intriguing popularizing works such as “Blondes in Venetian Paintings, the Nine-banded Armadillo, and Other Essays in Biochemistry”. He died in 2000, at the age of 88. In 1986, the annual Konrad Bloch lecture was inaugurated in his honor.

The author wishes to express his gratitude to Prof. Guido Guidotti for reviewing the text for accuracy.

The Bloch lecture, sponsored by Pfizer, honors Harvard faculty member and Nobel-prize recipient Konrad Bloch (1912-2000), a pioneer in the field of cholesterol and lipid metabolism.